This invention relates generally to systems for producing signals responsive to the identification and location of a detectable event, and more particularly, to a system for monitoring and counting scintillation events in each of multiple samples simultaneously, employing a position-sensitive detector.
There exist numerous applications where it is desirable to evaluate certain characteristics of a sample, or multiple samples, to monitor the concentrations of radioactivity. For example, a cell harvester collects multiple labeled discrete precipitates on a flat sheet, and can have as many as 96 samples. It is desired that detectable events in each sample be counted independently, with little scatter from neighboring samples. Moreover, there is a need for an instrument which can count:
(a) a single sheet of impregnated matrix containing solid scintillant and multiple discrete radioactive samples, such as are deposited by a Brandell Harvester;
(b) individual Beckman caps; or
(c) liquid scintillation vials using transparent tops.
Preferably, some 100 samples should be counted simultaneously.
There is additionally a need for an arrangement which can evaluate the patterns of radioactive proteins, illustratively in acrylamide gel slabs. Presently, autoradiographic means are employed to evaluate the radioactive proteins in acrylamide gel slabs. The known system is time-consuming, and not generally quantitative. In an application where such gels of about 20 cm by 20 cm are impregnated with fluor, whereby the distribution of radioactivity which is detected is measured and displayed on a CRT as it is collected, it is desirable to have high resolution. Current techniques for localization of the two-dimensional pattern of radioactivity rely upon autoradiography, wherein dried labeled gel is placed in contact with a photographic emulsion for extended periods, usually on the order of days to months, depending on the amount and energy of the radioactivity present. The results are not quantitative unless extensive calibration has first been performed with radioactive standards, or if the resulting autoradiogram is used as a guide for the excision of hot spots from the gel, followed by digestion of the samples, which are then counted in scintillation vials by standard techniques. If the radioactivity to be determined originates from tritium, it is necessary to impregnate the labeled gel with a fluor, so that a signal will reach the film emulsion before it is absorbed. These procedures are time-consuming, labor-intensive, and unquantitative, all of which establish a pronounced need for a new technology. Since the radioactivity is contained primarily inside the transparent gel, and does not reach the gel surface, position-sensing proportional counters are not useful for this application.
There is additionally a need for a system which can measure scintillation in a silica gel and other varieties of thin-layer chromatography, such as paper, glass, and other varieties of fiber matrices, such as are used in one and two-dimensional matrix chromatographic and electrophoretic separation. In these applications, the radioactivity is present on the surface of beads or fibers, and therefore the use of position-sensitive proportional gas flow counters is somewhat more appealing than in the case of gels. Nevertheless, flow counters leave much to be desired in that they are low in terms of counting efficiency and accuracy of quantification. In a typical system, substances which have been migrated by one- or two-dimensional chromatography are evaluated by scraping TLC plates, cutting paper, or exposing the intact plate or paper chromatogram to film. These known techniques, however, do not provide quick results or yield a quantitative analysis.
In the field of molecular biology, DNA/RNA hybridization is evaluated by blotting from a gel electrophorogram onto nitrocellulose, followed by autoradiography. The known technique, however, is time-consuming and does not yield accurate quantitative results. Additionally, there is a need to increase the speed with which new clones are detected, and to facilitate subtraction paradigms in which two or more two-dimensional samples are compared.
A still further area where there is a need for improved counting statistics is in the field of flow cells. As is known, counting accuracy is improved upon increasing the duration of the interval during which counting is performed. In essence, there is a need to increase the effective residence time of a radioactive, peak volume.
It is, therefore, an object of this invention to provide a simple and economical system for monitoring detectable events in a plurality of specimen samples.
It is another object of this invention to provide a system which can count detectable events in each of a plurality of neighboring samples, while eliminating the effect of the neighboring samples.
It is also an object of this invention to provide a system which can count detectable events in multiple discrete radioactive samples.
It is a further object of this invention to provide a system which can count detectable events in individual samples, such as Beckman caps.
It is additionally an object of this invention to provide a system which can count detectable events in liquid scintillation vials.
It is yet a further object of this invention to provide a system which can count detectable events in some one hundred samples simultaneously.
It is also another object of this invention to provide a system which can monitor the two-dimensional distribution of radioactivity in gel slabs.
It is yet an additional object of this invention to provide a system which can quantitatively analyze radioactive protein in acrylamide gel slabs.
It is still another object of this invention to provide a system which can rapidly and quantitatively count detectable events in silica gel and other thin layer chromatographic arrangements.
It is a yet further object of this invention to provide a system which can easily and quickly evaluate nucleic acid hybridization, and yield quantitative results.
It is also a further object of this invention to provide a system which can detect new clones during DNA/RNA hybridization, and facilitate subtraction paradigms.
It is additionally another object of this invention to provide a system which can be used in flow cell to increase the effective residence time of a radioactive slug, and thereby improve the accuracy of the event count.
A still further object of this invention is to provide a system which simply and economically achieves reliable scintillation counting of small samples.